Genetic tracing of Nav1.8-expressing vagal afferents in the mouse.
Genetic tracing of Nav1.8-expressing vagal afferents in the mouse.
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DOI：
10.1002/cne.22667
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发表时间：
2011-10-15
影响因子：
2.5
通讯作者：
Elmquist, Joel K.
中科院分区：
文献类型：
--
作者：
Gautron, Laurent;Sakata, Ichiro;Udit, Swalpa;Zigman, Jeffrey M.;Wood, John N.;Elmquist, Joel K.
Nav1.8是一种河豚毒素抗性钠通道，存在于外周感觉神经元的大子集中，包括脊髓和迷走神经传入。在脊髓传入神经中，Nav1.8在不同类型疼痛的信号传递中起着关键作用。然而，关于Nav1.8表达迷走神经元的确切身份和作用知之甚少。在这里，我们产生了在所有表达Nav1.8的传入神经元中限制表达tdTomato荧光蛋白的小鼠。结果，在这些神经元的细胞体、中枢中继和感觉末梢中可见强烈的荧光，揭示了它们在胸部和腹部内脏中的神经支配部位的全部范围。例如，迷走神经和脊髓Nav1.8表达的结束，分别清楚地看到胃肠道粘膜和肌间神经丛。在胃肠道肌肉壁中，标记的末梢包括一小部分迷走神经张力受体，但不包括任何牵张受体。我们还检查了关键代谢组织如肝脏和胰腺的详细神经支配，并评估了表达Nav1.8的迷走神经传入与选择的肠内分泌细胞（即，生长素释放肽、胰高血糖素、GLP-1）。具体来说，我们的数据显示，Nav1.8表达迷走神经传入神经在几个代谢组织和不同程度的接近Nav1.8表达粘膜传入神经和肠内分泌细胞，包括明显的神经内分泌沉积的存在。总之，这项研究证明了Cre-LoxP技术追踪确定的内脏传入神经的能力和多功能性，我们的数据表明Nav1.8表达迷走神经元在胃肠道功能中的作用以前未被认识。
Nav1.8 is a tetrodotoxin-resistant sodium channel present in large subsets of peripheral sensory neurons, including both spinal and vagal afferents. In spinal afferents, Nav1.8 plays a key role in signaling different types of pain. Little is known, however, about the exact identity and role of Nav1.8-expressing vagal neurons. Here we generated mice with restricted expression of tdTomato fluorescent protein in all Nav1.8-expressing afferent neurons. As a result, intense fluorescence was visible in the cell bodies, central relays, and sensory endings of these neurons, revealing the full extent of their innervation sites in thoracic and abdominal viscera. For instance, vagal and spinal Nav1.8-expressing endings were seen clearly within the gastrointestinal mucosa and myenteric plexus, respectively. In the gastrointestinal muscle wall, labeled endings included a small subset of vagal tension receptors but not any stretch receptors. We also examined the detailed inner-vation of key metabolic tissues such as liver and pancreas and evaluated the anatomical relationship of Nav1.8-expressing vagal afferents with select enteroendocrine cells (i.e., ghrelin, glucagon, GLP-1). Specifically, our data revealed the presence of Nav1.8-expressing vagal afferents in several metabolic tissues and varying degrees of proximity between Nav1.8-expressing mucosal afferents and enteroendocrine cells, including apparent neuroendocrine apposition. In summary, this study demonstrates the power and versatility of the Cre-LoxP technology to trace identified visceral afferents, and our data suggest a previously unrecognized role for Nav1.8-expressing vagal neurons in gastrointestinal functions.
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DOI：
10.1083/jcb.144.2.325
发表时间：
1999-01-25
期刊：
The Journal of cell biology
影响因子：
--
作者：
Esni F;Täljedal IB;Perl AK;Cremer H;Christofori G;Semb H
通讯作者：
Semb H
DOI：
10.1002/cne.22221
发表时间：
2010-01-01
期刊：
The Journal of comparative neurology
影响因子：
--
作者：
Gautron L;Lee C;Funahashi H;Friedman J;Lee S;Elmquist J
通讯作者：
Elmquist J
影响因子：
29.4
作者：
Date, Y;Murakami, N;Nakazato, M
通讯作者：
Nakazato, M
影响因子：
2.5
作者：
BERTHOUD, HR;JEDRZEJEWSKA, A;POWLEY, TL
通讯作者：
POWLEY, TL
影响因子：
2.7
作者：
Fox, Edward Alan
通讯作者：
Fox, Edward Alan